biostudies-literatureUnknown114(1)Iwasa SOno PharmaceuticalEP4, a prostaglandin E₂ receptor, has shown an immunosuppressive activity on cancer cells. This first-in-human study evaluated ONO-4578, a highly selective EP4 antagonist, as monotherapy and in combination with nivolumab in patients with advanced or metastatic solid tumors. A daily dose ranging from 30 mg to 100 mg of ONO-4578 monotherapy and that ranging from 2 mg to 60 mg of ONO-4578 with biweekly nivolumab 240 mg were administered. A total of 31 patients were enrolled, 10 receiving monotherapy and 21 receiving combination therapy. Overall, 26 patients experienced treatment-related adverse events. Dose-limiting toxicities were observed in three patients; one of six patients receiving 100 mg monotherapy developed grade 3 duodenal ulcer and two of six patients receiving 60 mg coCancer science211-220https://www.ebi.ac.uk/biostudies/studies/S-EPMC9807514biostudies-literatureFirst-in-human study of ONO-4578, an antagonist of prostaglandin E₂ receptor 4, alone and with nivolumab in solid tumors.PMC9807514Yamamoto NFujiwara YKoyama TShimizu TYoshida TShimomura ATamura KYonemori KIida HIwasa SNishino MKondo SYokoyama FKondo MSudo KKitano SSato JfalseFirst-in-human study of ONO-4578, an antagonist of prostaglandin E₂ receptor 4, alone and with nivolumab in solid tumors.EP4, a prostaglandin E₂ receptor, has shown an immunosuppressive activity on cancer cells. This first-in-human study evaluated ONO-4578, a highly selective EP4 antagonist, as monotherapy and in combination with nivolumab in patients with advanced or metastatic solid tumors. A daily dose ranging from 30 mg to 100 mg of ONO-4578 monotherapy and that ranging from 2 mg to 60 mg of ONO-4578 with biweekly nivolumab 240 mg were administered. A total of 31 patients were enrolled, 10 receiving monotherapy and 21 receiving combination therapy. Overall, 26 patients experienced treatment-related adverse events. Dose-limiting toxicities were observed in three patients; one of six patients receiving 100 mg monotherapy developed grade 3 duodenal ulcer and two of six patients receiving 60 mg co2023-01-01T00:00:00Z2023 Jan2026-05-27T21:05:02.175Z2024-11-14T18:56:41.013ZS-EPMC98075143608261610.1111/cas.15574